Introduction: Methamphetamine (Meth) and Buprenorphine (BUP) modulate pain perception. However, the antinociceptive effects of the interactions of these two substances, which belong to different systems, in rats, are unclear. The purpose of this study was to compare the analgesic effects of Meth, BUP, and their coadministration, and the effect of withdrawal from these substances on nociception in male rats.Methods: In this experiment, 40 male Wistar rats (250–300 g) were categorized into four groups: control, Meth, BUP, or BUP+Meth. After seven days of once-a-day treatments, the antinociceptive effects were assessed using the hot plate and the tail-flick tests. The differences among the groups were analyzed with ANOVA and Tukey's post hoc tests, and p values less than 0.05 were considered significant.Results: Meth and BUP increased the reaction times during the hot plate and tail-flick tests. The combination of Meth and BUP increased reaction time more than Meth and BUP alone.Discussion: The significantly high reaction times in rats treated with Meth and BUP indicate that these substances have antinociceptive effects. In addition, Meth enhanced the antinociceptive effects of BUP. These synergistic effects might occur through the dopaminergic, serotonergic, and/or adrenergic systems.